Crossregulation of β-catenin/Tcf pathway by NF-κB is mediated by lzts2 in human adipose tissue-derived mesenchymal stem cells

β-catenin/Tcf and NF-κB signaling pathways play an important role in biological functions and crosstalk between these pathways has been reported.  We found that the modulation of NF-κB activity showed a direct correlation with β-catein/Tcf pathway in human adipose tissue (hASCs) and bone marrow (hBMSCs)-derived mesenchymal stem cells. Expression of lzts2, which inhibits nuclear translocation of β-catenin and its transactivation activity, was regulated by NF-κB activity. Downregulation of lzts2 by RNA interference increased the nuclear translocation of β-catenin and NF-κB activity in hASCs. NF-κB activation by the downregulation of lzts2 was accompanied by the increase of β-TrCP1 expression and the decrease of IκB level. Downregulation of lzts2 increased the proliferation of hASCs and hBMSC, and blocked the NF-κB inhibitor-induced inhibitory effect on their proliferation and Tcf promoter activation. These findings provide the first evidence that the reciprocal crosstalk between β-catenin/Tcf pathway and NF-κB signaling in hMSCs is mediated through the regulation of lzts2 expression.